Concept and practical set-up of CFR, FFR, IMR Zsolt Piróth MD Gottsegen György Hungarian Institute of Cardiology

We all love coronary angiography, but Intermediate lesions (30-70%) Ostial lesions Left main coronary artery disease Diffusely diseased vessels Complex lesions Sequental lesions Loose relationship between angiography and prognosis Even best flat panel has resolution limited to 3 line pairs per mm, i. e. 9 line pairs or 9 pixels for a 3 mm vessel Coronary arteries are notoriously hard to image sharply: they are small and mobile.

Limitations of coronary angiography Circulation 1995; 92: 2333-42

What else than morphology? What kind of a physiologic parameter truly reflects the impact of a stenosis? Blood flow? – no meaning w/o the extent of perfusion area Flow derived parameters? – dependent on perfusion pressure Transstenotic gradient? – coronary blood flow is often not representative of myocardial flow

So, who do we believe? Complaints of pt Non-invasive tests Courtesy of Attila Kónyi, MD

The ideal parameter Reflects Severity of the stenosis in the subepicardial coronary artery (PCI) Amount of myocardium perfused by the diseased vessel Full myocardial perfusion, including collaterals Inducible ischemia FFR

FFRmyo Circulation 1993; 87: 1354-67

Definition of FFRmyo FFRmyo … is defined as the ratio of maximal achievable flow in the myocardium supplied by the stenotic vessel to the maximal achievable flow in the same territory in the hypothetical case that the vessel were normal. Circulation 1995; 92: 39-46

Mathematics of FFRmyo E = mc2 Assumptions: Resistances are constant and minimal CVP is negligible E = mc2

Characteristics of FFRmyo Specific index of the lesion in the subepicardial vessel „Pullback curve” conveys unparalelled spatial resolution Independent form HR, BP and contractility Normal value is 1,0 always and in all coronaries Well defined cut-off value: (0,75 - ) 0,80 Reflects collaterals Accounts for the amount of myocardium perfused by the vessel Applicable both in single vessel disease and MVD (no need for normal reference vessel) Measurement is simple, safe and possible in 99% of cases NHJ Pijls, B de Bruyne (eds): Coronary Pressure

Evaluating FFRmyo Sensitivity: 90% Specificity: 100%

Practical assets of FFRmyo Helpful in the indication of PCI Helps to avoid unnecessary interventions Identifies the „culprit lesion” Quality control of PCI, giving some prognostic implications Highly reproducible Relatively cheap, easy to perform, steep learning curve NHJ Pijls, B de Bruyne (eds): Coronary Pressure

Practice of measuring FFRmyo Standard preparation for PCI (TF/TR, venous access, anticoagulation, optimal GC, Y-connector) Set-up of Radi Analyzer® / Ilumien® / Quantien ® Flush PW, connect to interface then calibrate Zero aortic pressure signal Equalize pressure signals (Pa and Pd) when PW sensor is at the tip of the GC /preferably in the aorta/ Advance PW across the stenosis Induce MAXIMAL hyperemia (do not forget Ngl!) Measure FFR, perform pullback recording if necessary Perform PCI if indicated /possibility of measuring Pw, may not need any other guidewire/ Check post PCI FFR, perform pullback recording if necessary After pulling back the PW to the tip of the GC verify absence of pressure drift

Some practical tips Incorporate Analyzer into cath lab equipment (no nuisance to measure anymore) Perform measurement systematically, step-by-step Do it always the same way Act according to the result (do not discredit your own measurement) Make your coworkers understand what you are doing (assistants, surgeons...) If possible, get access to adenosine infusion for i. v. administration

FFR in critical anatomy ZI (Mrs. Tough MI Pt) 53-year-old lady Hx: hypertension, type II diabetes mellitus, s/p nephrectomy March 4, 2006: anterior STEMI (3 hrs) Coronary angiography Echo: LVH, good LVF, anterior akinesis w/o thinning

ZI Tecnic 3,0x15 mm RCA PCI of the LAD

ZI RAO cranial AP

Should we intervene? Courage trial NEJM 2007; 356: 1503-1516

Importance of ischemia Courage trial: 314 pt w/NPS Circulation 2008; 117: 1283- 1291

ZI: Left coronary artery 140 μg/kg/min iv adenosine

ZI: Right coronary artery 140 μg/kg/min iv adenosine

ZI No further treatment Pt continues to be symptom-free

Pull-back recording By inducing long-lasting hyperemia, one may slowly pull the PW back under fluoroscopy and determine how different segments of the vessel (lesions) contribute to the resistance to flow. By doing this, we are offered a lesion-specific index of ischemia By contrast, exercise ECG can be considered patient-specific (unable to determine ischemia localization), SPECT can be held vessel-specific. If an ischemic FFR value is obtained, and revascularisation is performed, FFR should be remeasured thereafter, because fixing one lesion may unmask the physiological significance of another.

Two compartments Epicardial Artery Microvasculature FFR IMR CFR

General principle of coronary thermodilution: F= V/Tmn One word on CFR General principle of coronary thermodilution: F= V/Tmn Since CFR= Fhyp/Fbas CFR= Tmnbas/Tmnhyp PW sensor acts as distal thermistor, PW shaft proximal thermistor Mean transit times measured by 3 brisk injections of 3 ml saline Issues with CFR: Highly dependent on resting flow Not specific for epicardial stenosis Normal value not clearly defined Distance of the sensor from GC tip is important Large sidebranches just proximal to distal stenosis GC position crucial (stable but not too deep)

IMR= Pd x Tmn at maximal hyperemia R= Pd-Pv/flow Since Flow ≈ 1/Tmn IMR= Pd/(1/Tmn) IMR= Pd x Tmn at maximal hyperemia Practical set-up identical to measuring simultaneous FFR and CFRthermo Limitations: Somewhat dependent on distance of PW down the vessel Clinical value not established

Measurement of IMR IMR = Pd x Th = 78 x 0,12 = 9,36